ENST00000475503.1:n.108G>A

Variant names:

• chr3-21405844-G-A
• rs409974
• ENST00000475503.1:n.108G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000475503.1(VENTXP7):​n.108G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0959 in 825,252 control chromosomes in the GnomAD database, including 4,533 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.12 (1216 hom., cov: 32)
  • Exomes 𝑓: 0.090 (3317 hom.)
• Consequence: VENTXP7 ENST00000475503.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.100
• Publications: 4 publications found

Genes affected

VENTXP7 (HGNC:13638): (VENT homeobox pseudogene 7) Homeobox genes encode DNA-binding proteins, many of which are thought to be involved in early embryonic development. Homeobox genes encode a DNA-binding domain of 60 to 63 amino acids referred to as the homeodomain. This pseudogene is a member of the Vent homeobox gene family. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VENTXP7	NR_002311.1	n.119G>A		non_coding_transcript_exon_variant	Exon 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VENTXP7	ENST00000475503.1	n.108G>A		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18687 AN: 151888 Hom.: 1217 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.0946

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.000588

Gnomad SAS AF: 0.0477

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.0446

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.107

GnomAD4 exome AF: 0.0898 AC: 60455 AN: 673246 Hom.: 3317 Cov.: 9 AF XY: 0.0879 AC XY: 31001 AN XY: 352668

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0898 AC: 1506 AN: 16768

American (AMR) AF: 0.0533 AC: 1533 AN: 28784

Ashkenazi Jewish (ASJ) AF: 0.0868 AC: 1548 AN: 17830

East Asian (EAS) AF: 0.000345 AC: 11 AN: 31908

South Asian (SAS) AF: 0.0364 AC: 2173 AN: 59774

European-Finnish (FIN) AF: 0.101 AC: 3171 AN: 31296

Middle Eastern (MID) AF: 0.0555 AC: 142 AN: 2560

European-Non Finnish (NFE) AF: 0.105 AC: 47337 AN: 450998

Other (OTH) AF: 0.0910 AC: 3034 AN: 33328

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.123 AC: 18687 AN: 152006 Hom.: 1216 Cov.: 32 AF XY: 0.116 AC XY: 8635 AN XY: 74288

African (AFR) AF: 0.123 AC: 5087 AN: 41484

American (AMR) AF: 0.0945 AC: 1445 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 402 AN: 3466

East Asian (EAS) AF: 0.000590 AC: 3 AN: 5086

South Asian (SAS) AF: 0.0479 AC: 231 AN: 4822

European-Finnish (FIN) AF: 0.108 AC: 1140 AN: 10600

Middle Eastern (MID) AF: 0.0445 AC: 13 AN: 292

European-Non Finnish (NFE) AF: 0.148 AC: 10032 AN: 67946

Other (OTH) AF: 0.106 AC: 223 AN: 2108

Alfa AF: 0.137 Hom.: 185

Bravo AF: 0.121

Asia WGS AF: 0.0310 AC: 109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.7
DANN	Benign	0.72
PhyloP100		0.10

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs409974; hg19: chr3-21447336;